Allele-Specific MicroRNA-Binding Variants at Colorectal Cancer Risk Loci in a Hispanic/Latino Population: An Integrative GWAS, All of Us, and Epigenomic Analysis
Abstract
Colorectal cancer (CRC) disproportionately affects Hispanic individuals, who remain underrepresented in genomic discovery and lack ancestry-matched functional resources. Many CRC risk variants are non-coding, and those in 3′ untranslated regions (3′ UTRs) can alter microRNA (miRNA) binding sites and reprogram post-transcriptional gene regulation. Here, we identify allele-specific miRNA-binding variants at CRC risk loci within the Hispanic population using a discovery pipeline anchored to Hispanic-relevant resources. CRC-associated 3′ UTR variants were compiled from the GWAS Catalog, further verified in Hispanic/Latino individuals using the All of Us Research Program cohort (n = 453), expanded into proxy sets using Admixed American-specific linkage disequilibrium, annotated against Ensembl transcripts, and evaluated with TargetScan and RNAhybrid. Screening of 38 CRC-associated 3′ UTR SNPs identified 19 variants that alter miRNA binding across nine genes, with each gene represented by a variant confirmed in the Hispanic cohort. Three oncogenic loci, DCBLD2 (lead SNP rs11552978), GREM1 (lead SNP rs10318), and SMC1B (rs3747239, prioritized as an AMR-specific proxy in near-complete LD with confirmed lead rs6007600), met all prioritization criteria. In each case, the risk allele disrupts a strong miRNA-binding site, while the gene shows increased tumor expression, weak correlation between expression and methylation, and an absence of local active transcriptional chromatin marks…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 453 participants or records.
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